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  • Title: Transport of cimetidine across the basolateral membrane of rabbit kidney S2 proximal tubules.
    Author: Brändle E, Greven J.
    Journal: Arch Int Pharmacodyn Ther; 1991; 314():169-85. PubMed ID: 1824187.
    Abstract:
    The aim of the present study was to characterize the cellular cimetidine uptake at the basolateral membrane of isolated nonperfused S2 tubular segments by exchange transport studies. Therefore, all tubules were firstly preincubated for 25 min with 2 x 10(-7) mol/l [3H]cimetidine. After the uptake of cimetidine had achieved a state of equilibrium, nonradiolabelled cimetidine was added to the incubation medium and the time course of the change in intracellular amount of [3H]cimetidine was measured. After application of unlabelled cimetidine, in a concentration of 10(-6) mol/l and 5 x 10(-5) mol/l, the cellular amount of radiolabelled cimetidine decreased to 30.9 +/- 2.7% and 24 +/- 2.1% of the control value, respectively. This new state of equilibrium was achieved after approximately 15 min in both experiments. In the exchange experiments of [3H]cimetidine with 10(-2) mol/l KCN, the cellular content of cimetidine decreased to 40% of the control value. On the other hand, ouabain, applied 25 min after preincubation, reduced the intracellularly accumulated cimetidine concentration to 17.5 +/- 2% of the control value. Quinine, tetraethylammonium and procainamide, in a concentration of 5 x 10(-5) mol/l, reduced the intracellular amount of [3H]cimetidine to 26.4 +/- 6.8%, 51.6 +/- 6.7% and 48.3 +/- 5.5% of the control value, respectively. After application of choline (10(-3) mol/l) and N1-methylnicotinamide (10(-3) mol/l), a new state of equilibrium of 37 +/- 4.5% and 64.2 +/- 3.5% of the control value was achieved. Na-citrate (10(-3) M) had no effect on the intracellular [3H]cimetidine concentration. These cimetidine exchange studies suggest that cimetidine is transported via a carrier, probably the cation transport system, at the basolateral membrane into the cells of kidney S2 proximal tubular segments.
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